help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology, doi:10.1210/en.2003-0693
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
144/12/5347    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prunet-Marcassus, B.
Right arrow Articles by Pénicaud, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prunet-Marcassus, B.
Right arrow Articles by Pénicaud, L.
Endocrinology Vol. 144, No. 12 5347-5352
Copyright © 2003 by The Endocrine Society

Melatonin Reduces Body Weight Gain in Sprague Dawley Rats with Diet-Induced Obesity

Bénédicte Prunet-Marcassus, Mathieu Desbazeille, Arnaud Bros, Katie Louche, Philippe Delagrange, Pierre Renard, Louis Casteilla and Luc Pénicaud

Unité Mixte de Recherche 5018, Centre National de la Recherche Scientifique, Université Paul Sabatier, Institut Fédératif de Recherche 31 (B.P.-M., M.D., A.B., K.L., L.C., L.P.), Centre Hospitalier Universitaire Rangueil, 31059 Toulouse Cedex 9, France; and Institut de Recherche International Servier (P.D., P.R.), Courbevoie 92415, France

Address all correspondence and requests for reprints to: Dr. Luc Pénicaud, Unité Mixte de Recherche 5018-Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire Rangueil, bâtiment L1, 1 avenue J. Poulhès, 31059 Toulouse Cedex 9, France. E-mail: penicaud{at}toulouse.inserm.fr.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Melatonin is involved in the regulation of seasonal obesity in various species, including some rodents. This involvement has been demonstrated in nonphotoperiodic rodents like rats, but only in models of enhanced body weight such as genetically obese or middle-aged rats. The aim of this investigation was to determine the effects of melatonin on body weight and metabolic parameters in a model closer to that observed in Western populations, i.e. Sprague Dawley rats fed a high-fat diet. They were treated for 3 wk with melatonin (30 mg/kg) 4 h after lights-on [Zeitgeber time (ZT) 4] or 1 h before lights-out (ZT11). Given at ZT11, melatonin decreased body weight gain and feed efficiency by half. Melatonin had no effect on plasma insulin level, but it decreased plasma glucose (13%), leptin (28%), and triglyceride (28%) levels. Furthermore, in pinealectomized high-fat diet rats, body weight gain and feed efficiency were increased 4 wk after surgery. Adipose tissue weight, insulinemia, and glycemia had a tendency to increase. Treatment with melatonin prevented in part these changes. These data demonstrate that melatonin may act as a regulator of body weight in a model of obesity and may prevent some of the side effects on glucose homeostasis such as decreased insulin sensitivity.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
MELATONIN IS A neurohormone synthesized and secreted at night mainly by the pineal gland in vertebrates (1, 2). It affects various physiological functions such as seasonal reproduction, thermoregulation, and energy metabolism in mammals and particularly in seasonal mammalian species. In the latter, melatonin is known to affect body mass, adiposity, and both energy intake and expenditure (3, 4, 5, 6). These effects may vary according to the species. Thus, opposite results are observed in Siberian and Syrian hamsters, in which melatonin decreases or increases body fat mass, respectively (4, 7). Furthermore, a melatonin agonist and antagonist stimulates or lowers seasonal obesity in the garden dormouse (8). The exact mechanism of action is not yet fully understood. A direct effect of melatonin on brown adipocytes (9) and an indirect effect via the sympathetic nervous system (10, 11) have both been demonstrated.

Although these effects are less clear in nonphotoperiodic species, there are reports suggesting such a role for melatonin in rats. In obese Zucker rats raised in a long photoperiod, body mass was heavier than in those maintained in a short photoperiod, whereas lean rats were not sensitive to these changes (12). More directly, whereas in young adult Wistar rats body weight was not affected by continuous light or melatonin treatment (13), melatonin has been shown to decrease body weight in middle-aged rats (14, 15).

Taken overall, these data suggest that melatonin has no effect in rats with normal body weight but that it alters body fat mass which is already elevated, as in aging or genetically obese rats. The present study was undertaken to test this hypothesis in a model considered to be relevant in human species, i.e. diet-induced obesity. Rats were fed a high-fat diet (HFD) until they were overweight and were then treated with melatonin or pinealectomized. Body weight and metabolic parameters were determined.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Animals
Male Sprague Dawley rats (5–7 wk old) purchased from a commercial supplier (Charles River Laboratories, Les Oncins, France) were individually housed in standard plastic cages. The light cycle was 12-h light and 12-h darkness, with lights-off at 1900 h. Rats were kept in a temperature-controlled room (21 C). Food and water were available ad libitum. All procedures were performed in accordance with Principles of Laboratory Animal Care (NIH publication 86-23, revised 1985) as well as with French national law.

HFD
Rats were fed from weaning until the beginning of the experiment with a standard high-carbohydrate diet (HCD; 3.81 kcal/g; 229H, UAR, Villemoisson, France) composed of 64.2% carbohydrate, 30.7% protein, and 5.1% fat. They were then randomly divided into two groups. One group was kept on the same HCD, whereas the other group was fed with a HFD (5.35 kcal/g, 231H, UAR) composed of 17.4% carbohydrate, 42.9% protein, and 39.7% fat. The animals were weighed three times a week until the average body weight reached a significant difference of at least 20 g between the two groups. They were then treated according to the protocols described below.

Melatonin administration
Melatonin (Sigma Chemical Co., St. Louis, MO) was administered daily by gavage for 3 wk (200 µl/100 g, 30 mg/kg) to HFD rats either 4 h after lights-on (ZT4, n = 15) or 1 h before lights-off (ZT11, n = 16). A group of HFD rats (n = 14) and a group of HCD rats (n = 9) received solvent (0.5% hydroxyethylcellulose and 1% Tween 80, Sigma Chemical Co.). Animals and food were weighed every day at ZT3.

To determine whether melatonin affected food intake, 20 rats were fed with HFD for 1 wk. Half of the rats were treated (single administration) with melatonin (30 mg/kg), and the other half with solvent at ZT11. Food was weighed 4 h and 24 h after treatment.

Pinealectomy
Twenty HFD rats were pinealectomized, and 11 HFD rats were sham-operated as described elsewhere (16). Rats were anesthetized with pentobarbital (6 mg/100 g). A square skull flap was incised to expose the sinus confluence. The transverse and sagittal sinuses were ligated. One sinus was cut, and the confluence was raised to expose the pineal gland, which was removed with curved forceps. The sham operation consisted of a similar procedure without removal of the pineal gland. After recovery from surgery, rats were treated with either solvent (n = 10) or melatonin at ZT 11 (n = 10) for 3 wk, as described above. Body weight and food were weighed each day for 3 wk.

Decapitation and dissection
Rats were killed by decapitation between 0800 and 1300 h. Blood was collected, and plasma was stored at -80 C. Interscapular brown adipose tissue, epididymal, and inguinal white adipose tissues were dissected and immediately weighed.

Hormonal and biochemical parameter measurements
Plasma insulin and leptin levels were determined using commercial RIA kits from Diasorin (Paris, France) and Clinisciences (Linco Research, Inc., St. Charles, MO), respectively. Glycemia was measured with a blood glucose sensor (Glucotrend 2, Roche, Basel, Switzerland), and triglycerides were measured using a fully enzymatic determination kit (BioMérieux, Marcy-l’Etoile, France).

Calculations and statistical analyses
Body weight gain changes were analyzed by two-way ANOVA comparing treatment and time effects. All results are given as means ± SEM. Student’s t test or Bonferroni’s test were applied when two or more values respectively were compared. The statistical software used was Graphpad Prism version 2.0 for Windows (GraphPad Software, San Diego, CA).

Feed efficiency was calculated as grams of body weight gain per kilocalorie of food eaten over 3 wk (melatonin treatment) or 4 wk (pinealectomy).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
Changes in body weight and food consumption
To establish the HFD obesity model, the aim was a minimum difference of 20 g body weight between rats fed HCD compared with those fed HFD. As soon as this difference reached significance (P < 0.05), HFD rats were treated with solvent or melatonin (30 mg/kg) either 4 h after lights-on (ZT4) or 1 h before lights-off (ZT11) (Fig. 1AGo). A Bonferroni’s test analysis showed that body weight during the 3 wk of treatment was significantly lower in HFD rats treated with melatonin at ZT11 than in HFD rats treated with solvent (P < 0.001; Fig. 1BGo). The difference in body weight gain became significant as soon as d 5 after the beginning of the treatment. When melatonin was administered at ZT4, the Bonferroni’s test did not reveal an effect of the treatment (Fig. 1BGo). At the end of the treatment, body weight of HFD rats treated with melatonin at ZT11 was reduced by 5.1%. Food consumption was unchanged in all groups of HFD rats during the study (total food intake in kilocalories over the 21 d was: solvent, 1845 ± 61; ZT4, 1822 ± 29; and ZT11, 1697 ± 49). However, feed efficiency was increased in HFD rats and was decreased by melatonin, whatever the administration time (Fig. 1CGo).



View larger version (34K):
[in this window]
[in a new window]
  		FIG. 1. Effect of melatonin administration on body weight and feed efficiency of rats fed HFD. A, Schematic protocol. Sprague Dawley rats were fed either a HCD or a HFD and treated with solvent 4 h after lights-on (ZT4). Two groups of HFD rats were treated with melatonin (30 mg/kg) at either ZT4 or ZT11 (1 h before lights-off). B, Evolution of body weight during melatonin administration. Values are means + SEM and were analyzed by two-way ANOVA excluding the HCD group. There was a significant effect of treatment and time on body weight (P < 0.001), without interaction between the two variables. Analysis with Bonferroni’s test shows: HFD melatonin ZT11 vs. HFD (P < 0.05). C, Feed efficiency over the 3 wk of melatonin administration. Values are means ± SEM and were analyzed by Bonferroni’s test. **, P < 0.01; ***, P < 0.001.

 
Final body weight gain and adipose tissues
After 3 wk of treatment, HFD resulted in a significant increase of body weight (48%) and of inguinal and epididymal white adipose tissue as well as brown adipose tissue mass. Interscapular brown adipose tissue mass was decreased significantly by melatonin treatment at ZT11 (Table 1Go). Daily melatonin administration at ZT4 and ZT11 decreased the body weight gain of HFD rats by 25 and 54%, respectively (Table 1Go). Although the treatment tended to lower adipose tissue mass, the decrease was not significant.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Effect of melatonin on body weight gain and fat pad mass in rats fed HFD

 
Acute effect of melatonin on food intake
To verify that melatonin had no effect on food intake, rats fed for 1 wk with HFD were given a single dose of either solvent or melatonin (30 mg/kg) at ZT11. Food consumption was similar in the two groups after 4 h (8.3 ± 0.8 and 7.1 ± 0.5 g, respectively) as well as after 24 h (20.8 ± 0.6 and 20.5 ± 0.7 g, respectively).

Metabolic and hormonal parameters
When compared with HCD, HFD had no significant effect on plasma glucose and triglyceride levels (Fig. 2Go). Plasma insulin (2.17 ± 0.15 vs. 1.80 ± 0.11 ng/ml) and leptin (7.16 ± 0.67 vs. 4.32 ± 0.74 ng/ml) were significantly increased. Melatonin treatment had no significant effect on insulinemia, whatever the time of administration. However, glycemia (82 ± 3 and 70 ± 1 mg/dl), leptinemia (7.16 ± 0.67 and 5.14 ± 0.52 ng/ml), and plasma triglyceride levels (0.81 ± 0.06 and 0.59 ± 0.06 g/liter) were significantly decreased when melatonin was given at ZT11.



View larger version (13K):
[in this window]
[in a new window]
  		FIG. 2. Effect of melatonin administration on metabolic and hormonal parameters. Sprague Dawley rats fed HCD were treated with solvent, and animals fed HFD were treated with solvent (HFD) or melatonin (30 mg/kg) at either ZT4 or ZT11 for 3 wk. Plasma glucose (A), triglycerides (B), insulin (C), and leptin (D) levels were assessed from blood of nonfasted rats. Values are means ± SEM and were analyzed by Bonferroni’s test. $$$, P < 0.001 vs. HCD, HFD, and HFD melatonin ZT4. *, P < 0.05; **, P < 0.01 vs. HC; +, P < 0.05 vs. HFD.

 
Effect of pinealectomy
The body weight of operated rats decreased for the first 2 d after surgery. The rats regained weight thereafter. The body weight gain during the 3 wk of the experiment was higher in pinealectomized (66 ± 4 g) than in sham-operated rats (49 ± 3 g) (Fig. 3AGo and Table 2Go). The difference in body weight became significant at d 8 after pinealectomy. Food consumption was similar in the two groups (data not shown). Figure 3BGo shows that feed efficiency was increased by 28% after pinealectomy. In pinealectomized rats treated with melatonin, body weight gain and feed efficiency were no longer different from sham-operated animals (Fig. 3Go and Table 2Go). Total caloric intake (kilocalories) over the 3-wk period was not significantly altered by pinealectomy (1815 ± 65 vs. 1745 ± 75 in sham-operated animals) but there was a net tendency toward a decrease when rats were treated daily by melatonin (1678 ± 65).



View larger version (18K):
[in this window]
[in a new window]
  		FIG. 3. Effect of pinealectomy with or without melatonin treatment (30 mg/kg daily at ZT11) on body weight gain in rats fed HFD. A, Graph shows means ± SEM of weight gain. Values were analyzed by two-way ANOVA; there was a significant effect of treatment (P < 0.001) and time (P < 0.001) on body weight gain, without interaction between the two variables. B, Feed efficiency over the period after pinealectomy. Values are means ± SEM and were analyzed by Student’s t test. *, P < 0.05.

 

View this table:
[in this window]
[in a new window]
  		TABLE 2. Effect of pinealectomy with or without melatonin treatment on body weight gain, adipose tissue mass, metabolic and hormonal parameters in rats fed HFD

 
Pinealectomy did not significantly alter the weight of brown and white fat pads, although there was a tendency toward an increase compared with sham-operated rats (Table 2Go). Similarly, plasma glucose and insulin levels were higher after pinealectomy, but this did not reach significance (Table 2Go). These tendencies disappeared in rats treated with melatonin (Table 2Go).


   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
The present study clearly demonstrates that melatonin is involved in body weight regulation in overweight animals. Two lines of evidence support this conclusion. First, rats with increased body weight induced by a HFD and given a daily injection of melatonin for 3 wk gained significantly less weight than control rats on the same diet. Second, the regulatory role of melatonin is reinforced by the results from the pinealectomized rats because the absence of melatonin induces increased body weight that disappears when animals where supplemented with the neurohormone. Our observation of the ability of melatonin to lower body weight is consistent with recent papers demonstrating this effect in both middle-aged rats treated by melatonin (14, 15) and obese Zucker rats exposed to short photoperiod, a condition known to increase melatonin exposition (12). The decrease in body weight from 5 to 6% in 3 wk is relatively similar in all three models. Melatonin appears to act only when energy balance is disturbed, because such effects were not obtained when treatment, as well as pinealectomy, was performed in normal rats (13, 17). Furthermore, we demonstrated that melatonin efficiency was time dependent. The increased effect of melatonin when administered before the end of the light period (ZT11) could be explained by 1) greater sensitivity to melatonin at the time of administration due to an increased density of melatonin receptor (18, 19), or 2) longer duration of high melatonin level. Indeed, we cannot rule out that the effect of melatonin on body weight is completely independent of its chronobiotic properties. Nevertheless for both times of administration, we observed an effect on the food efficiency.

One might be concerned by the high melatonin dosage (30 mg/kg) used in the present investigation. This was justified because we wanted to get a prolonged effect, considering the short half-life of melatonin, the fact that it was given by gavage as a unique dose and that rats are less sensible than photoperiodic animals. Indeed, most of the studies concerning the effect of melatonin on body weight regulation have been performed using melatonin infusion, implants, or melatonin in water (15, 20).

The effect on body weight was achieved despite the fact that melatonin treatment apparently did not influence food intake, in agreement with previous observations (12, 14, 15). This, together with a lower feed efficiency, suggests changes in energy metabolism and in the ability to store excess energy as body fat. This is consistent with previous reports on melatonin effects on physical activity and metabolic rate. Thus, melatonin has been reported to reverse decreased physical activity induced by age or continuous light exposure (15, 21, 22). On the other hand, it has been shown that melatonin injections increased norepinephrine-stimulated nonshivering thermogenesis (23). The decrease we observed in the weight of brown adipose tissue is in line with such an effect, which could be either direct or indirect via activation of the sympathetic nervous system (9, 24).

Although melatonin-treated rats tended to have lower whole body fat mass, this decrease was not obvious when comparing specific fat deposits. In previous works, melatonin was shown to decrease fat pads and, more specifically, visceral deposits without affecting sc fat (14, 15). The lack of change in our study could be due to 1) the shorter period of treatment, because in the latter studies melatonin impregnation lasted at least 10 wk against 3 wk in the present work; or 2) the mode of melatonin administration, because we gave melatonin once a day and not in the drinking water. Once again, the effect of melatonin on the fat pad mass, if any, could be due to activation of the sympathetic nervous system and its consequences in terms of lipolysis and adipose tissue plasticity (24, 25). In contrast to its weak effect on adipose tissue mass, melatonin quite markedly reduced plasma leptin levels. Rasmussen et al. (14) have shown in aged rats that in addition to inducing decrease in fat mass, melatonin lowered plasma leptin levels. Exogenous melatonin administration to pinealectomized rats reversed the increased plasma leptin levels observed 2 months after surgery without related changes in body fat (26). Taken overall, these data demonstrate that the effect of melatonin on plasma leptin level is not entirely correlated with changes in body mass. This could suggest a direct effect on the secretory capacity of adipose cells.

Melatonin effects on glucose homeostasis are somewhat contradictory in normal rats (17, 27), although a recent report supports that it might increase glucose tolerance and insulin secretion (28). In models with altered body weight, such as middle-aged (15) and obese rats (12), as well as in the present study of overweight rats, results indicate that melatonin may improve insulin sensitivity. Thus, in the two former models, it significantly decreased plasma insulin levels without corresponding changes in plasma glucose. We found blood glucose was significantly lowered without change in plasma insulin level when melatonin was administered before lights-off. On the other hand, pinealectomy did not significantly modify either parameter. The apparent effect on insulin sensitivity seen in the present study, as well as lower plasma triglycerides, could be due to the lower body weight. This would be consistent with the fact that both were mainly observed in the rats treated at ZT11 and with numerous data demonstrating the parallelism between these variables (29, 30).

In conclusion, we demonstrated that melatonin may act as a regulator of body weight in a model of overweight similar to that observed in Western populations. Not only is the neurohormone able to limit the body weight gain induced by HFD, but it also appears to prevent some of the side effects on lipid metabolism and on glucose homeostasis, such as decreased insulin sensitivity. It was noteworthy that these effects of melatonin were possibly time dependent.


   Acknowledgments
 
We thank Dr. L. Ambid for helpful discussions, Dr. S. Pellissier for technical advice, and J. M. Lerme for animal care.


   Footnotes
 
This research was generously supported by the Institut de Recherche International Servier, in particular by providing fellowships to B.P.-M., M.D., A.B., and K.L.

B.P.-M. and M.D. contributed equally to this work.

Abbreviations: HCD, High-carbohydrate diet; HFD, high-fat diet; ZT, Zeitgeber time.

Received June 3, 2003.

Accepted for publication September 5, 2003.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Arendt J 1995 Melatonin and the mammalian pineal gland. London: Chapman and Hall; 201–285
  2. Reiter RJ 1991 Pineal melatonin: cell biology of its synthesis and of its physiological interactions. Endocr Rev 12:151–180[CrossRef][Medline]
  3. Himms-Hagen J 1984 Nonshivering thermogenesis. Brain Res Bull 12:151–160[CrossRef][Medline]
  4. Wade GN, Bartness TJ 1984 Photoperiod and diet effects on obesity in hamsters. Am J Physiol 247:R328–R334
  5. McElroy JF, Wade GN 1986 Short photoperiod stimulates brown adipose tissue growth and thermogenesis but not norepinephrine turnover in Syrian hamsters. Physiol Behav 37:307–311[CrossRef][Medline]
  6. Bartness TJ 1995 Short day-induced depletion of lipid stores is fat pad- and gender-specific in Siberian hamsters. Physiol Behav 58:539–550[CrossRef][Medline]
  7. Bartness TJ, Wade GN 1985 Photoperiodic control of seasonal body weight cycles in hamsters. Neurosci Biobehav Rev 9:599–612[CrossRef][Medline]
  8. Le Gouic S, Delagrange P, Atgié C, Nibbelink M, Hanoun N, Casteilla L, Renard P, Lesieur D, Guardiola-Lemaitre B, Ambid L 1996 Effects of both a melatonin agonist and antagonist on seasonal changes in body mass and energy intake in the garden dormouse. Int J Obes 20:661–667
  9. Prunet-Marcassus B, Ambid L, Viguerie-Bascands N, Pénicaud L, Casteilla L 2001 Evidence for a direct effect of melatonin on mitochondrial genome expression of Siberian hamster brown adipocytes. J Pineal Res 30:108–115[CrossRef][Medline]
  10. McElroy JF, Mason PW, Hamilton JM, Wade GN 1986 Effects of diet and photoperiod on NE turnover and GDP binding in Siberian hamster brown adipose tissue. Am J Physiol 250:R383–R388
  11. Youngstrom TG, Bartness TJ 1995 Catecholaminergic innervation of white adipose tissue in Siberian hamsters. Am J Physiol 268:R744–R751
  12. Larkin LM, Moore BJ, Stern JS, Horwitz BA 1991 Effect of photoperiod on body weight and food intake of obese and lean Zucker rats. Life Sci 49:735–745[Medline]
  13. Mustonen AM, Nieminen P, Hyvärinen H 2002 Effects of continuous light and melatonin treatment on energy metabolism of the rat. J Endocrinol Invest 25:716–723[Medline]
  14. Rasmussen DD, Boldt BM, Wilkinson CW, Yellon SM, Matsumoto AM 1999 Daily melatonin administration at middle age suppresses male rat visceral fat, plasma leptin, and plasma insulin to youthful levels. Endocrinology 140:1009–1012[Abstract/Free Full Text]
  15. Wolden-Hanson T, Mitton DR, McCants RL, Yellon SM, Wilkinson CW, Matsumoto AM, Rasmussen DD 2000 Daily melatonin administration to middle-aged male rats suppresses body weight, intraabdominal adiposity, and plasma leptin and insulin independent of food intake and total body fat. Endocrinology 141:487–497[Abstract/Free Full Text]
  16. Bonouali-Pellissier S 1994 Melatonin is involved in cholecystokinin-induced changes of ileal motility in rats. J Pineal Res 17:79–85[Medline]
  17. Lima FB, Machado UF, Bartol I, Seraphim PM, Sumida DH, Moraes SM, Hell NS, Okamoto MM, Saad MJ, Carvalho CR, Cipolla-Neto J 1998 Pinealectomy causes glucose intolerance and decreases adipose cell responsiveness to insulin in rats. Am J Physiol 275:E934–E941
  18. Morgan PJ, Barrett P, Howell HE, Helliwell R 1994 Melatonin receptors: localization, molecular pharmacology and physiological significance. Neurochem Int 24:101–146[CrossRef][Medline]
  19. Vanecek J 1998 Cellular mechanisms of melatonin action. Physiol Rev 78:687–721[Abstract/Free Full Text]
  20. Bartness TJ, Powers JB, Hastings MH, Bittman EL, Goldman BD 1993 The timed infusion paradigm for melatonin delivery: what has it taught us about the melatonin signal, its reception and the photoperiodic control of seasonal responses? J Pineal Res 15:161–190[Medline]
  21. Araghi-Niknam M, Lane L, Watson RR 1999 Modification of physical movement in old C57BL/6 mice by DHEA and melatonin supplementation. Proc Soc Exp Biol Med 221:193–197[Abstract]
  22. Depres-Brummer P, Metzger G, Levi F 1998 Pharmacologic restoration of suppressed temperature rhythms in rats by melatonin, melatonin receptor agonist, S20242, or 8-OH-DPAT. Eur J Pharmacol 347:57–66[CrossRef][Medline]
  23. Hall ES, Lynch GR 1985 Two daily melatonin injections differentially induce nonshivering thermogenesis and gonadal regression in the mouse (Peromyscus leucopus). Life Sci 37:783–788[CrossRef][Medline]
  24. Bartness TJ, Demas GE, Song CK 2002 Seasonal changes in adiposity: the roles of the photoperiod, melatonin and other hormones, and sympathetic nervous system. Exp Biol Med 227:363–376[Abstract/Free Full Text]
  25. Pénicaud L, Cousin B, Leloup C, Lorsignol A, Casteilla L 2000 The autonomic nervous system, adipose-tissue plasticity, and energy balance. Nutrition 16:903–908[CrossRef][Medline]
  26. Canpolat S, Sandal S, Yilmaz B, Yasar A, Kutlu S, Baydas G, Kelestimur H 2001 Effects of pinealectomy and exogenous melatonin on serum leptin levels in male rat. Eur J Pharmacol 428:145–148[CrossRef][Medline]
  27. Bizot-Espiard JG, Doublé A, Cousin B, Lesieur D, Guardiola-Lemaître B, Delagrange P, Ktorza A, Pénicaud L 1998 Lack of melatonin effects on insulin action in normal rats. Horm Metab Res 30:711–716[Medline]
  28. La Fleur SE, Kalsbeek A, Wortel J, der Vliet J, Buijs RM 2001 Role for the pineal and melatonin in glucose homeostasis: pinealectomy increases night-time glucose concentrations. J Neuroendocrinol 13:1025–1032[CrossRef][Medline]
  29. Ghibaudi L, Cook J, Farley C, van Heek M, Hwa JJ 2002 Fat intake affects adiposity, comorbidity factors, and energy metabolism of Sprague-Dawley rats. Obes Res 10:956–963[Medline]
  30. Carmena R, Ascaso JF, Real JT 2001 Impact of obesity in primary hyperlipidemias. Nutr Metab Cardiovasc Dis 11:354–359[Medline]



This article has been cited by other articles:


Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Sanchez-Hidalgo, Z. Lu, D.-X. Tan, M. D. Maldonado, R. J. Reiter, and R. I. Gregerman
Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells: implications for osteoblast differentiation and osteoporosis
Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2007; 292(6): R2208 - R2215.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. I. C. Alonso-Vale, S. Andreotti, S. B. Peres, G. F. Anhe, C. das Neves Borges-Silva, J. C. Neto, and F. B. Lima
Melatonin enhances leptin expression by rat adipocytes in the presence of insulin
Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E805 - E812.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
144/12/5347    most recent
Author Manuscript (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Prunet-Marcassus, B.
Right arrow Articles by Pénicaud, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Prunet-Marcassus, B.
Right arrow Articles by Pénicaud, L.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals